In this project it is proposed to purify the phenotypic variants of alpha-1-antitrypsin (alpha 1-at) by affinity chromatography, to ascertain the structural differences in the proteins which account for phenotypic variation, to quantitatively characterize the biochemical and biological activity of each purified variant and attempt to relate this to known disorders associated with alpha-1-antitrypsin deficiencies in man. An attempt will be made to investigate the nature of alpha 1-at complex with a variety of human serum proteolytic enzymes with which it has been shown to react, and to determine whether phenotypic variants of alpha 1-at exhibit identical reactivity. It is hoped that such a structural and biochemical analysis of purified alpha 1-at will provide information about biological properties and activity of alpha 1-at in vitro as well as in vivo.